Chemical analyzer

ABSTRACT

An automatic chemical analyzer in which a reaction solution is stirred by air ejected from an air ejection hole placed above a reaction container. The reaction region can be washed and cleaned sufficiently without causing damage, such as exfoliation of a coating reagent. A reaction container disk is provided with a pore and a pressure detector connected with the pore. Before and after the stirring operation, the ejection hole (nozzle) ejecting air is moved and the output value of the pressure detector is compared with a previously measured normal value. With a discharge pipe and a suction pipe inserted to the opening of the reaction container to be close to both ends of the opening and the side wall of the container, the reaction region at the bottom of the container is washed by continuous discharge and suction of cleaning fluid.

This application is a divisional of U.S. patent application Ser. No.13/201,491, filed Aug. 15, 2011.

TECHNICAL FIELD

The present invention relates to a chemical analyzer suitable foranalysis of trace substances contained in a living organism.

BACKGROUND ART

An automatic analyzer for qualitative/quantitative analyses ofbiological samples (blood, urine, etc.) performs such an analysis thatthe color of reaction solution is changed due to reaction of a reagentwith analysis-target constituents in a sample (colorimetric analysis).Such an automatic analyzer also performs such an analysis that markersare added directly or indirectly to substances that react specificallywith the analysis-target constituents and the number of the markers iscounted (immunity analysis), etc. In the automatic analyzer describedabove, stirring the mixed solution after mixing of the sample and thereagent is effective for promoting the reaction. For reaction between aliquid sample and a liquid reagent, the stirring of the reactionsolution is conducted generally by use of a stir bar or the likeinserted into the reaction container. However, the use of the stir barcan become impossible when the amount of the reaction solution is small.A technique for stirring reaction solution in a reaction container byuse of air ejected from a nozzle is described in Patent Literatures 1and 2.

After the reaction is completed, suction of the reaction solution iscarried out to remove the unreacted surplus sample from the reactioncontainer. Thereafter, in order to enhance the sample removing effect,the reaction container is washed with a cleaning fluid as needed.

Such an analyzer is described in Patent Literature 3, for example.

PRIOR ART LITERATURE Patent Literature

-   Patent Literature 1: JP-2007-51863-A-   Patent Literature 2: JP-6-39266-A-   Patent Literature 3: JP-7-83939-A

SUMMARY OF THE INVENTION Problem to be Solved by the Invention

In the stirring by use of a stir bar, whether the reaction solution isbeing stirred successfully or not can be checked with ease since thestir bar is immersed in the reaction solution and rotates in thereaction solution during the stirring operation. In contrast, when themechanism for stirring the reaction solution with ejected air is used,it is difficult to check whether or not the stirring is being conductedas expected. Even when there is an abnormality in a measurement valueobtained by the analysis, it is difficult to judge whether there was anabnormality in the sample or insufficient stirring of the reactionsolution led to the abnormal result.

It is therefore an object of the present invention to provide a chemicalanalyzer having a mechanism for stirring a reaction solution by ejectingair from an air ejection hole and achieving high reliability of analysisresult by making it possible to check whether the stirring mechanism isoperating normally.

Further, in an analyzer using the aforementioned reaction container,removing the unreacted surplus sample from the reaction containersufficiently is essential for high-accuracy analysis. However, if thesupply of the cleaning fluid to the reaction container or the suction offluid from the reaction container is conducted at a high flow velocityto remove the surplus sample, there is the danger of exfoliation of acoating reagent from the reaction container coated with the reagent.Even though the analyzer described in the Patent Literature 3 carriesout the supply of the cleaning fluid or the suction of fluid byinserting a discharge pipe and a suction pipe to the reaction container,the above problem had not been recognized yet.

It is therefore another object of the present invention to provide achemical analyzer capable of achieving high analysis accuracy and highdevice reliability by sufficiently washing and cleaning the reactioncontainer without causing any problem (e.g., exfoliation of the coatingreagent on the bottom of the reaction container in cases where thereaction container is in a flat dish-like shape).

Means for Solving the Problem

A chemical analyzer in accordance with the present invention forresolving the above problems is configured as follows:

A chemical analyzer comprising: a reaction container setting table onwhich a plurality of reaction containers each having an opening are set;and an air ejection hole for ejecting air to the opening of the reactioncontainer, wherein at least one selected from a pressure sensor, atemperature sensor and a humidity sensor is provided at a positionbetween reaction container setting positions on the reaction containersetting table.

Preferably, the reaction container setting table is provided with a poreand a pressure sensor connected with the pore. Before or after thestirring operation, the ejection hole ejecting air is stopped or movedover the pore, the output value of the sensor at the time of thestoppage/movement of the ejection hole is monitored, and the outputvalue is compared with a previously acquired signal value in a normalstate.

Another chemical analyzer in accordance with the present invention isconfigured as follows:

A chemical analyzer comprising: a reaction container having an openingand a reaction region situated at the center of the reaction container'sbottom; a cleaning fluid discharge pipe for discharging cleaning fluidto the reaction container; and a suction pipe for sucking fluid out ofthe reaction container, wherein the chemical analyzer comprises acontrol mechanism which controls washing of the reaction container sothat: the suction pipe is lowered to the opening of the reactioncontainer prior to the discharge pipe and starts the suction of fluid,and the discharge pipe is subsequently lowered to the opening of thereaction container and discharges the cleaning fluid, and the suction offluid and the discharge of the cleaning fluid are conducted concurrentlyfor at least a prescribed time period.

Effect of the Invention

In a chemical analyzer having a mechanism for stirring a reactionsolution by ejecting air from an air ejection hole, the check on whetherthe stirring mechanism is operating normally is made possible.Consequently, a chemical analyzer with high reliability of analysisresult can be provided.

Another effect of the present invention is as follows:

A chemical analyzer with high analysis accuracy and high devicereliability can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overall schematic diagram of a chemical analyzer inaccordance with an embodiment of the present invention.

FIG. 2 is a schematic diagram of an incubator unit in the embodiment ofthe present invention.

FIG. 3 is a schematic diagram of the incubator unit in the embodiment ofthe present invention.

FIG. 4 is a schematic diagram showing the arrangement of nozzles andpores in the embodiment of the present invention.

FIG. 5(A) shows an example of an output of one pressure detecting meansin the embodiment of the present invention.

FIG. 5(B) shows an example of an output of another pressure sensordetecting means in the embodiment of the present invention.

FIG. 5(C) shows an example of an output of another pressure sensordetecting means in the embodiment of the present invention.

FIG. 6 is a schematic diagram of an incubator unit in an embodiment ofthe present invention.

FIG. 7 shows an example of the output of temperature detecting means inthe embodiment of the present invention.

FIG. 8 shows an example of the output of a load sensor in the embodimentof the present invention.

FIG. 9 is a schematic diagram of an incubator unit in an embodiment ofthe present invention.

FIG. 10(A) is a schematic diagram showing arrangements of a nozzle diskand a flushing disk during a stirring operation in the embodiment of thepresent invention.

FIG. 10(B) is a schematic diagram showing arrangements of a nozzle diskand a flushing disk during a flushing operation in the embodiment of thepresent invention.

FIG. 11 is an overall schematic diagram of a chemical analyzer inaccordance with an embodiment of the present invention.

FIG. 12 is a schematic diagram of a washing mechanism in the embodimentof the present invention.

FIG. 13 is a flow chart of a washing operation in the embodiment of thepresent invention.

FIG. 14 is a schematic diagram showing central cross sections of areaction container, a discharge pipe and a suction pipe for explainingthe washing of the reaction container in the embodiment of the presentinvention.

FIG. 15 is a schematic diagram showing central cross sections of areaction container, a discharge pipe and a suction pipe for explainingthe washing of the reaction container in an embodiment of the presentinvention.

FIG. 16 is a schematic diagram showing central cross sections of areaction container, discharge pipes and a suction pipe for explainingthe washing of the reaction container in an embodiment of the presentinvention.

FIG. 17 is an enlarged view of a washing position shown in FIG. 11.

FIG. 18 is a schematic diagram for explaining the reaction container,the cleaning fluid discharge pipe, the suction pipe, a rinse chip andthe cleaning fluid flow in the washing operation in an embodiment of thepresent invention, wherein FIG. 18(A) is a central cross-sectional viewand FIG. 18(B) is a bottom view of the reaction container.

FIG. 19 shows flow velocity distribution on the central cross section ofthe reaction container in the washing operation in embodiments of thepresent invention.

FIG. 20 is a schematic diagram showing another embodiment of the presentinvention, wherein FIG. 20(A) is a cross-sectional view and FIG. 20(B)is a bottom view of the reaction container.

MODE FOR CARRYING OUT THE INVENTION

Referring now to the drawings, a description will be given in detail ofpreferred embodiments in accordance with the present invention.

First Embodiment

First, referring to FIGS. 1 to 3, the configuration of a chemicalanalyzer in accordance with a first embodiment of the present inventionwill be described. FIG. 1 is an overall schematic diagram of thechemical analyzer. FIG. 2 is a schematic perspective view showing theinside of an incubator unit. FIG. 3 is an explanatory drawingschematically showing the setup inside the incubator unit viewed fromthe side.

As shown in FIG. 1, the chemical analyzer comprises a carrier 101 forcarrying a small-sized reaction container 100, a sample disk 111 forstoring sample containers 110, a reagent disk 121 for storing reagentcontainers 120, a separate pouring mechanism 130 for pouring a sampleand a reagent separately from their respective containers to thereaction container 100, an incubator unit 140 for stirring a reactionsolution made up of the sample and the reagent, and an optical detectionmechanism 150 including an excitation light irradiator and afluorescence emission intensity detector. The incubator unit 140includes a reaction disk 161 having reaction container setting spots 160on which the reaction containers 100 can be set, a nozzle disk 171having nozzles 170 for ejecting compressed air, and a side wall 142surrounding the incubator unit.

As shown in FIG. 2, the nozzle disk 171 and the reaction disk 161 of theincubator unit 140 are components in disk-like shapes. The plurality ofnozzles 170 are provided along the circumference of the nozzle disk 171,while the plurality of reaction container setting spots 160 are providedalong the circumference of the reaction disk 161. The nozzles 170 andthe reaction container setting spots 160 are situated at positionscorresponding to each other in the vertical direction, respectively.Each reaction container 100 is placed under one of the nozzles 170. Thesample and the reagent in the reaction container 100 are stirred andmixed together by the compressed air ejected from the nozzle 170.

As shown in FIG. 3, the nozzle disk 171 and the reaction disk 161 aredriven by drive motors 231 and 232, respectively. The nozzle disk 171 issupplied with the compressed air from an air pump 202 via a filter 203for removing dust. A pipe pressure sensor 204 is attached to the wall ofa pipe 201. One of the reaction container setting spots 160 of thereaction disk 161 is provided with pores 240. A pressure sensor 241 ofthe diaphragm type (as pressure detecting means) is embedded in a partof the reaction disk 161 at the end of each pore 240.

These components automatically conduct an analysis with prescribedtiming as explained below based on previously inputted analysis iteminformation. First, the sample and the reagent are poured from separatecontainers to a reaction container 100 by the separate pouring mechanism130. Subsequently, the reaction container 100 is carried from anincubator unit opening 141 to the inside of the incubator by moving thecarrier 101 while rotating the reaction disk 161. The reaction container100 is set on a prescribed reaction container setting spot of thereaction disk 161 and the compressed air is ejected from the nozzle 170placed over the reaction container. The ejected compressed air collideswith the surface of the reaction solution made up of the sample and thereagent and thereby causes a stirring flow in the reaction solution, bywhich the sample and the reagent are stirred and mixed together. Thereaction container 100 after completion of the stirring is taken outfrom the incubator unit 140 and moved to a position under the detectionmechanism 150 by the carrier 101. At this position, optical detection isconducted to the reaction solution in the reaction container 100.

Before and after this analysis operation, the so-called“initialization”, including a check on whether each mechanism of thechemical analyzer operates normally or not and an operation forreturning each mechanism to its original position, is carried out. Inthe initialization, a nozzle abnormality detecting operation, forensuring normal operation of the stirring mechanism, is conducted. Inthe nozzle abnormality detecting operation, the reaction containersetting spots 160 are empty as shown in FIG. 3. The nozzles shown inFIG. 3 are numbered from #1 to #5, for example.

FIG. 4 is a schematic diagram showing the positions of the nozzlesprojected onto the reaction disk for explaining the movement of thenozzles and the positional relationship among the nozzles, the pore,etc. In this embodiment, three pores 240 a, 240 b and 240 c are arrangedin a line orthogonal to the rotation direction 310 of the nozzles. Thedotted line 802 indicates a circumference on the nozzle disk 171 onwhich the nozzles 170 are provided. Static pressure sensors 241 a, 241 band 241 c are connected to the pores and output signals 341 a, 341 b and341 c, respectively. The pore 240 b is placed at the central positionregarding the nozzle movement 310 and the pores 240 a and 240 c areplaced the same distances apart from the central position. In FIG. 4,positions 170(2), 170(3) and 170(4) of nozzles #2, #3 and #4, among themany nozzles 170, are indicated. FIG. 4 shows a situation in which thenozzle #2 has shifted from its normal position and dust 350 has adheredto the nozzle #4 as will be explained below.

FIG. 5 shows an example of the outputs of the pressure sensors, whereinthe horizontal axis of each graph represents time and the vertical axisof each graph represents signal intensity of the output of each pressuresensor. (A), (B) and (C) of FIG. 5 indicate outputs 341 a, 341 b and 341c of the three pressure sensors shown in FIG. 4, respectively. Thecompressed air ejected from the nozzle 170 forms a colliding jet flowover the reaction disk 161. Due to the nature of the colliding jet flow,the pressure on the reaction disk (as the collision surface) is thehighest at the position right under the nozzle and decreases with theincrease in the distance from the nozzle. Thus, if the nozzle disk 171is moved while continuing the ejection of the compressed air from thenozzle 170, the pressure displays periodic variations corresponding tothe nozzles #1-#5 since the pressure reaches a maximum when a nozzle 170passes right above the pore 240, thereafter decreases, and increasesagain when the next nozzle passes over the pore 240. The output 341 b ofthe sensor 241 b (connected to the pore 240 b formed right under thetrack of the nozzles) is the highest among the outputs of the threesensors. The outputs 341 a and 341 c are lower than the output 341 b andequivalent to each other due to the symmetry. When the stirringmechanism is in its normal state, the output of each pressure sensortakes on the same value for all the nozzles as indicated by the solidline 401 in FIG. 5.

The maximum values of the outputs are A0, B0 and C0, respectively. Thesevalues will hereinafter be referred to as “normal values”.

First, an example of nozzle abnormality will be explained, in which thenozzles #1, #2, #3 and #5 are in their normal states but the nozzle #4has turned to a clogged nozzle 170(4) due to the dust 350 adheringthereto as shown in FIG. 4. The dust 350 in the nozzle #4 has formed asa secular variation due to accumulation of dust (particles) smaller thanthe mesh size of the filter 203. The output value of each sensor in thiscase is indicated with a dotted line 410 in FIG. 5. All the outputs 341a, 341 b and 341 c drop at time corresponding to the nozzle #4, themaximum values of the outputs 341 a, 341 b and 341 c corresponding tothe nozzle #4 are A1, B1 and C1, respectively. The output profiles alsobecome blunt. The output values regarding the other nozzles of thenozzle disk have not changed substantially from the solid lines. Theoccurrence of an abnormality (clogging) to the nozzle #4 can be found asabove from such output values different from the normal values.

Next, another example of nozzle abnormality will be explained, in whichthe nozzles #1, #3, #4 and #5 are in their normal states but theposition of the nozzle #2 has shifted as indicated with the referencecharacter 170(2) in FIG. 4. The output value of each sensor in this caseis indicated with a chain line 420 in FIG. 5. The parts (periods) of theoutput values 341 a, 341 b and 341 c corresponding to the passage of thenozzles #1, #3, #4 and #5 remain on the solid lines 401 (normal values).However, due to the shift of the nozzle #2 toward the sensor 241 aindicated with the reference character 170(2) in FIG. 4, maximum valuesA2, B2 and C2 of the output values 341 a, 341 b and 341 c correspondingto the nozzle #2 satisfy the relationship A2>B2>C2. The occurrence ofthe displacement (misalignment) of the nozzle #2 can be found as abovefrom such output values different from the normal values. Suchdisplacement detection works in the same way not only in cases where theposition of a single nozzle has shifted but also in cases where theposition of the reaction disk or the nozzle disk has shifted.

When the result described above is obtained by the pressure measurementbefore or after a stirring operation, the analysis using the nozzle #2or #4 is considered to be under the influence of stirring conditionsdifferent from those of the other nozzles, and thus the reliability ofthe analysis result using the nozzle #2 or #4 is low. Therefore, thedevice operation program (analyzer operation program) is modified so asnot to use the nozzles #2 and #4 from the next analysis. It is possibleto previously determine the lowest permissible pressure (greatestpermissible pressure change) capable of avoiding substantialdeterioration in the stirring performance as performance data of theanalyzer, store the lowest permissible pressure in the analyzer'sprogram as a normal value, and compare the output value with the storednormal value. The normal value may be stored as a continuous profilewith a high sampling frequency, or it is also possible to output asignal with a low sampling frequency in sync with the nozzle diskdriving frequency and use a discrete value (maximum value, minimumvalue, etc.) of the signal as the normal value. An analysis resultobtained by using an abnormal nozzle for the stirring operation may beindicated on the user interface so as to let the user request thesupplier of the device (analyzer) to perform the maintenance. It is alsopossible to provide an LED lamp nearby each nozzle and light the LEDlamp when an abnormality has occurred to the nozzle. This realizes highmaintainability since the personnel performing the check and maintenancehas only to check and clean the abnormal nozzle while disregarding theother nozzles.

As shown in the pressure sensor output examples of FIG. 5, the peaks,etc. of the output value of each pressure sensor are detected atprescribed times if the stirring mechanism is operating normally. If thetimes of the peaks, etc. have deviated from the prescribed times, thereis a possibility of an abnormality in the drive motor 231 for rotatingthe nozzle disk 171. In such cases, maintenance of the drive motor 231is desired to be performed.

While the abnormality detecting operation described above may beperformed before and after each analysis, the abnormality detectingoperation may be performed only at the startup and shutdown of thedevice (analyzer), or only when the pipe pressure sensor 204 indicatedan abnormal value.

While the pores 240 are provided in only one reaction container settingspot 160 in this embodiment in consideration of the restriction on thedevice space, detection of pressure leaking out during the stirringoperation becomes possible if the pores 240 are provided in the spacesbetween the reaction container setting spots 160. Further, while thethree pores 240 and the three sensors 241 are provided at one reactioncontainer setting spot 160 in this embodiment, the detection of a nozzleabnormality based on a change in the sensor output value is possibleeven with only one pair of pore 240 and sensor 241. It is also possibleto provide every reaction container setting spot 160 with the pores 240and the sensors 241, which is desirable since the need of moving thenozzle disk 171 for the abnormality detecting operation is eliminated.

Furthermore, while the pressure detection is carried out by rotating thenozzle disk 171 in this embodiment, equivalent effects can be achievedalso by rotating the reaction disk 161.

Second Embodiment

FIG. 6 is an explanatory drawing schematically showing the setup insidean incubator unit similarly to FIG. 3. A heater 501 and a humidifier 502are provided in the middle of the pipe 201 connecting the air pump 202to the nozzle disk 171, with which the temperature and humidity in theincubator are kept constant. A temperature sensor 510 is placed inmidair inside the incubator at a position between two reaction containersetting spots 160 so as not to obstruct the stirring operation. Thetemperature sensor 510 monitors the temperature inside the incubatorduring the stirring operation.

In the initialization operation before or after the stirring operation,if the nozzle disk 171 is rotated while the compressed air is ejectedfrom all the nozzles 170, the jets of the compressed air ejected fromthe nozzles 170 successively pass over the temperature sensor 510. FIG.7 shows an example of the output value of the temperature sensor 510 inthis case, wherein the horizontal axis represents time and the verticalaxis represents the output value. The output value repeats increasingand decreasing at fixed periods in response to the passage of thenozzles #1-#5. Even when the inside of the incubator unit 140 is kept ata temperature T1, the temperature of the compressed air just after beingejected from the nozzle is higher than T1 since the compressed air hasjust been heated by the heater. Therefore, the output value of thetemperature sensor 510 repeats increasing and decreasing in a fixedpattern between the minimum value T1 and a maximum value T2 as indicatedby the solid line 601 if the nozzles are in their normal states.However, if an abnormality such as the displacement or the clogging (dueto adhesion of dust) has occurred to the nozzle #4, for example, asexplained in the previous embodiment referring to FIG. 4, theincrease/decrease pattern changes (e.g., the maximum value decreases toT3) as indicated by the broken line 602. The nozzle abnormality can bedetected by comparing the change (changed value) with the normal value.Incidentally, equivalent effects can be achieved by using a humiditysensor instead of the temperature sensor. It is possible to provide aplurality of sensors similarly to the first embodiment, which isdesirable since the amount of acquirable information increases. It isalso possible to provide a sensor at every interval between adjoiningreaction container setting spots 160, which is more desirable since theamount of acquirable information increases further.

Meanwhile, one of the reaction container setting spots 160 is equippedwith a load sensor 520 as shown in FIG. 6 so that the load on thereaction container 100 set on the reaction container setting spot 160can be detected. The reaction container 100 receives force when thecompressed air is applied to the reaction solution during the stirringoperation. FIG. 8 shows an example of a graph representing the output ofthe load sensor 520, wherein the horizontal axis represents time and thevertical axis represents the load sensor output. When the nozzle abovethe load sensor is in the normal state, the output value of the loadsensor changes between a minimum value W1 and a maximum value W2 asindicated with the solid line 701. When the displacement or the cloggingwith adhering dust has occurred to the nozzle as shown in FIG. 4, theincrease/decrease pattern changes (e.g., the maximum value decreases toW3) as indicated with the broken line 702. Therefore, the nozzleabnormality can be detected in the midst of the stirring operation.Incidentally, while only one reaction container setting spot 160 isequipped with the load sensor 520 in this embodiment, it is possible toequip every reaction container setting spot 160 with the load sensor520. Such a configuration is desirable since the stirring status of allthe reaction containers 100 can be monitored.

Third Embodiment

FIG. 9 is an explanatory drawing schematically showing the setup insidean incubator unit similarly to FIG. 3. A flushing disk 801 is providedin a part of the nozzle disk 171 close to the nozzles 170. Theconnection between the flushing disk 801 and the nozzle disk 171 can beswitched by a key groove mechanism 810. By the switching, the flushingdisk 801 can either be driven together with the nozzle disk 171 by thedrive motor 231 or be separated from the nozzle disk 171 and fixedinside the incubator.

FIG. 10 shows the positional relationship among the nozzle disk 171, thenozzles 170, the flushing disk 801, etc. viewed from the reaction disk161, wherein FIG. 10(A) shows the positional relationship during thestirring operation and FIG. 10(B) shows the positional relationshipduring a flushing operation. The flushing disk 801 is a component in adisk-like shape, having a flushing through hole 851 and a plurality ofstirring through holes 850 formed on the same circumference 802. In thestirring operation, the flushing disk 801 and the nozzle disk 171 rotatetogether. The compressed air to be ejected from the nozzles 170 passesthrough the stirring through holes 850 (formed at positionscorresponding to the nozzles) to stir the reaction solutions.

In the initialization operation, the flushing of the nozzles (removal ofdust, etc. adhering to the nozzles) is carried out by letting a largeamount of air flow through the nozzles. In the flushing operation, onlythe nozzle disk 171 is rotated while fixing the flushing disk 801 in theincubator. As shown in FIG. 9 and FIG. 10(B), the compressed air isejected from only one nozzle 830 via the flushing through hole 851,while the other nozzles 170 are capped by the flushing disk 801 servingas strong fluid resistance. Therefore, even without the need of a highflow setting of the air pump 202, the flushing can be conductedsuccessfully since a large amount of air flows exclusively through thenozzle 830 connected with the flushing through hole 851. The flushingcan be conducted to all the nozzles since all the nozzles pass throughthe flushing through hole 851 along with the rotation of the nozzle disk171.

In a part of the reaction disk 161 under the flushing through hole 851,a deep hole 840 is formed so that the removed dust from the nozzles canbe stored therein.

During the flushing operation, the output of the pipe pressure sensor204 is monitored. The monitoring makes it possible to check whether thedust, etc. has been removed successfully from the nozzle 830 or notsince the output value increases when the clogging, etc. has occurred tothe nozzle 830 and returns to a certain level upon the removal of thedust, etc.

With the above configuration and operation, the clogging of the nozzlescan be eliminated. This embodiment implements the flushing of thenozzles at a lower cost in comparison with cases where a large amount ofair is let through all the nozzles at once by use of a high flow pump.This embodiment implements the flushing at a lower cost also incomparison with cases where each nozzle is equipped with a valve as ameans to block up each nozzle other than the nozzle 830.

Fourth Embodiment

FIG. 11 is an overall schematic diagram of a chemical analyzer inaccordance with a forth embodiment of the present invention. Thechemical analyzer comprises a sample disk 1011 for storing samplecontainers 1010, a reaction disk 1131 on which small-sized reactioncontainers 1140 are set, a separate pouring mechanism 1020 for pouringsamples separately to the reaction containers, a washing mechanism 1030for washing the reaction containers, a washing bath 1110 for washing thewashing mechanism, and an optical detection mechanism 1040 including anexcitation light irradiator and a fluorescence emission intensitydetector. The reaction disk 1131 is a component in a disk-like shape,having the plurality of reaction containers 1140 provided along itscircumference. These components operate automatically with prescribedtiming as explained below based on previously inputted analysis iteminformation. First, a sample is separately poured from the samplecontainer 1010 to the reaction container 1140 by the separate pouringmechanism 1020. Then, a chemical reaction starts in a reaction region atthe bottom of the reaction container. The reaction container in whichthe chemical reaction has completed is moved to a prescribed positionnearby the washing mechanism 1030 by the rotation of the reaction disk1131. At the position, the washing mechanism 1030 descends to thereaction container and washes the reaction container. The reactioncontainer after being washed is moved to a position under the detectionmechanism 1040 by the rotation of the reaction disk 1131. At theposition, the result of the reaction in the reaction region is detectedby the detection mechanism 1040.

FIG. 12 is a schematic diagram of the washing mechanism. The washingmechanism includes a washing head operation mechanism 1106 and thewashing bath 1110 provided on the base 1111 of the analyzer. The washinghead operation mechanism 1106 vertically moves and horizontally rotatesa washing head 1103, having a discharge pipe 1101 and a suction pipe1102 for the discharge and the suction of a cleaning fluid, as indicatedby the arrows 1104 and 1105. The washing bath 1110 is used for washingthe tips of the discharge pipe and the suction pipe. A cleaning fluidfeeding mechanism 1120, including a cleaning fluid tank and a dischargepump, is connected to the discharge pipe 1101 via piping 1121.Similarly, a cleaning fluid suction mechanism 1122, including a suctionpump and a waste fluid tank, is connected to the cleaning fluid suctionpipe 1102 via piping 1123. The arrows 1124 indicate the directions ofthe flow of the cleaning fluid. A washing pipe cleaning fluid feedingmechanism 1113 (including a cleaning fluid tank and a discharge pump forsupplying and discarding a washing pipe cleaning fluid 1112) and awashing pipe waste fluid suction mechanism 1114 (including a waste fluidtank and a suction pump) are connected to the washing bath 1110 (forwashing the tips of the discharge pipe 1101 and the suction pipe 1102)via piping 1115 and piping 1116, respectively. The arrows 1117 indicatethe directions of the flow of the washing pipe cleaning fluid.

FIG. 13 is a flow chart of the washing operation. When the reaction inthe reaction region is completed (S01 in FIG. 13), the reaction disk1131 is rotated first, by which the reaction container 1140 is moved tothe washing position (S02 in FIG. 13). Subsequently, the suction pump ofthe cleaning fluid suction mechanism 1122 is activated (S03 in FIG. 13)and the washing head 1103 is lowered with the suction pump ON (S04 inFIG. 13). Then, the suction of the reaction solution starts at theinstant that the tip of the suction pipe 1102 contacts the surface 1151of the reaction solution 1141 (S05 in FIG. 13). Since the cleaning fluidsuction unit (suction pump) is already in operation as above, thereaction solution is discharged from the reaction container first, bywhich the cleaning efficiency is improved compared to cases where thecleaning fluid mixed with the reaction solution is circulated in thereaction container. Further, if the washing pipes are soaked in thereaction solution when the reaction container is full of the reactionsolution, the reaction solution may overflow from the reactioncontainer, contaminate the analyzer, and deteriorate the reliability ofthe analyzer. This embodiment eliminates such a problem since thereaction solution has sufficiently been discharged from the reactioncontainer at the point when the lowering of the washing head iscompleted. After the lowering of the washing head 1103 is completed,discharge of the cleaning fluid from the discharge pipe 1101 is startedwhile continuing the suction through the suction pipe 1102 (S06 and S07in FIG. 13).

FIG. 14 is a schematic diagram showing central cross sections of thereaction container, the discharge pipe and the suction pipe forexplaining the washing of the reaction container at this stage. In FIG.14, the axis 1410 indicates positions on the central axis of thereaction container, the reference characters A and C represent both endsof the reaction region 1150, and the reference character B representsthe center of the reaction region. The discharge pipe 1101 and thesuction pipe 1102 are placed as close to the side wall of the reactioncontainer 1140 as possible so that the pipes 1101 and 1102 do notinterfere with the reaction region 1150. In this state, the cleaningfluid 1400 is discharged from the discharge pipe 1101 and sucked by thesuction pipe 1102 as indicated by the arrows 1124, by which a cleaningfluid flow indicated by the arrows 1401 a, 1401 b, 1401 c and 1401 d isformed in the reaction region 1150. As above, the suction of thecleaning fluid is carried out not after filling the reaction containerwith the cleaning fluid but concurrently with the discharge of thecleaning fluid from the discharge pipe 1101. This constantly forms thecleaning fluid flow at the bottom of the reaction container during thewashing operation, by which the reaction region can be washed andcleaned sufficiently.

FIG. 19 shows an example of flow velocity distribution of the cleaningfluid flow on the central axis of the bottom of the reaction container,wherein the horizontal axis represents the position in the reactioncontainer and the vertical axis represents the flow velocity. A flowvelocity range not harming the reaction region is between V1 and V2.Flow velocity lower than V1 lead to insufficient washing, while flowvelocity higher than V2 cause exfoliation in the reaction region. Theflow velocity distribution in this embodiment is indicated with a solidline 1801 in FIG. 19. The flow velocity 1401 a under the discharge pipe1101 is high since the cross-sectional area of the channel for thecleaning fluid formed between the tip of the discharge pipe and thebottom of the reaction container is small. However, the cleaning fluidflow does not harm the reaction region since the maximum flow velocitydoes not exceed V2 as indicated by the solid line 1801 in FIG. 19.Meanwhile, the flow velocity does not fall below V1 even at the minimumpoint B. Therefore, the reaction region can be washed and cleanedsufficiently. Incidentally, while the flow velocity distribution on thecentral axis is shown in FIG. 19, the flow velocity distribution hasbeen confirmed to be within the above flow velocity range throughout thebottom of the reaction container (the same goes for the followingembodiments).

Even after the discharge of a prescribed amount of cleaning fluid isfinished and the washing of the reaction region is completed, thesucking operation is continued (S08, S09 and S10 in FIG. 13), by whichthe cleaning fluid is totally sucked out of the reaction container. Ifsome of the cleaning fluid remains in the reaction container, opticalreflection may occur on the surface of the remaining fluid and thatdeteriorate the detection accuracy. Such a problem can be prevented bythe continuation of the sucking operation.

Thereafter, the washing head 1103 is raised, the sucking operation isended, and the reaction container 1140 is removed from the washingposition by rotating the reaction disk 1131 (S10, S11 and S12 in FIG.13). Meanwhile, the tips of the discharge pipe 1101 and the suction pipe1102 are inserted into the washing bath 1110 by rotating and loweringthe washing head 1103, the tips of the pipes 1101 and 1102 are washedwith the washing pipe cleaning fluid 1112 circulated in the washingbath, and the whole washing operation is finished (S12 in FIG. 13).

Fifth Embodiment

Another embodiment will be described below. FIG. 15 is a schematicdiagram showing the central cross sections of the reaction container, adischarge pipe and a suction pipe in the washing operation similarly toFIG. 14. In this embodiment, the tip of the suction pipe is placedcloser to the bottom of the reaction container compared to the tip ofthe discharge pipe. The position of the tip of the discharge pipe isdesired to be not higher than the opening of the reaction container asshown in FIG. 15 so that the cleaning fluid does not scatter aroundduring the washing.

The washing operation is performed as shown in FIG. 13. As the washinghead 1103 shown in FIG. 12 is lowered, only the tip of the suction pipe1102 makes contact with the reaction solution surface 1151 and thesuction of the reaction solution 1141 starts (S04 and S05 in FIG. 13).If the tips of the discharge pipe 1101 and the suction pipe 1102 are atthe same height, the tip of the discharge pipe 1101 also makes contactwith the reaction solution 1141 and is contaminated with the reactionsolution. Such a problem can be avoided by this embodiment.

When the lowering of the washing head is completed and the discharge ofthe cleaning fluid is started (S06 and S07 in FIG. 13), a flow of thecleaning fluid 1400 occurs at the bottom of the reaction container 1140as indicated with the arrows 1500 a, 1500 b, 1500 c and 1500 d in FIG.15.

If the amount of flow is increased in the fourth embodiment, the flowvelocity distribution changes to that indicated with the dotted line1802 in FIG. 19 and the flow velocity at the point A increases to V3higher than V2. However, in the case of FIG. 15 where the tip of thedischarge pipe is far apart from the bottom of the reaction container,the velocity of the flow 1500 a is low since the flow 1501 from thedischarge pipe is gradually decelerated by friction with surroundingcleaning fluid. In this case, the maximum velocity decreases and theflow velocity distribution fits in the range between V1 and V2 asindicated with the thick dotted line 1803 in FIG. 19. Thus, the reactioncontainer can be washed and cleaned sufficiently without harming thereaction region.

Subsequently, the discharge of the cleaning fluid is finished and onlythe suction is continued (S08 and S09 in FIG. 13). If the tip of thedischarge pipe is situated close to the bottom of the reaction containerat this stage, some cleaning fluid tends to remain in the reactionregion in spite of the suction due to adhesion to the part around thetip of the discharge pipe. In this embodiment, the discharge pipe is farapart from the bottom, and thus the problem (cleaning fluid left in thereaction region) can substantially be eliminated, contributing to thesecurement of high analysis accuracy.

Sixth Embodiment

Still another embodiment will be described below referring to FIGS. 12,13 and 16. FIG. 16 is a schematic diagram showing the central crosssections of the reaction container, discharge pipes and a suction pipein the washing operation similarly to FIG. 14.

In this embodiment, two discharge pipes and one suction pipe are used.The discharge pipes 1101 are placed at both ends of the reaction region1150, while the suction pipe 1102 is placed at the center of thereaction region 1150.

The washing operation is performed as shown in FIG. 13. When thelowering of the washing head 1103 shown in FIG. 12 is completed and thedischarge of the cleaning fluid is started (S06 and S07 in FIG. 13), aflow of the cleaning fluid 1400 occurs at the bottom of the reactioncontainer as indicated with the arrows 1600 a, 1600 b and 1600 c in FIG.16. The flow velocity distribution at this stage is indicated with achain line 1804 in FIG. 19. In this embodiment, however, the cleaningflow velocity is high even at the point B since the flow path of thecleaning fluid flow 1600 a, 1600 b, 1600 c is shorter than that in thecases where the discharge pipe and the suction pipe are placed at theends of the reaction region (e.g., embodiments 4 and 5). Even though theflow velocity drops at some points since the point B is like astagnation point where discharge flows from both sides collide with eachother, the flow velocity distribution fits in the range between V1 andV2. Thus, the reaction container can be washed and cleaned sufficientlywithout harming the reaction region. Conversely, by taking advantage ofthis relationship, it is possible to reduce the running cost bydecreasing the amount of flow, that is, decreasing the amount of thecleaning fluid used for the washing. The flow velocity distribution inthis case is indicated with a thick chain line 1805 in FIG. 19. Eventhough the maximum value has dropped to V5, the flow velocitydistribution is still within the range between V1 and V2. Thus, thereaction container can be washed and cleaned sufficiently withoutharming the reaction region.

Seventh Embodiment

Still another embodiment will be described below referring to FIGS. 12,13, 17 and 18. FIG. 17 is an enlarged view of the washing position shownin FIG. 11. FIG. 18 is a schematic diagram for explaining the reactioncontainer, a cleaning fluid discharge pipe, a suction pipe, a rinse chipand the cleaning fluid flow in the washing operation, wherein FIG. 18(A)is a central cross-sectional view and FIG. 18(B) is a bottom view of thereaction container. In this embodiment, a structure called “rinse chip1701”, serving as the top of the reaction container 1140, is attached tothe tips of the discharge pipe 1101 and the suction pipe 1102 as shownin FIG. 17.

The washing operation is performed as shown in FIG. 13. The cleaningfluid suction unit (suction pump) of the cleaning fluid suctionmechanism 1122 shown in FIG. 12 is activated (S03 in FIG. 13) and thewashing head 1103 is lowered into the reaction container 1140 with thesuction pump ON (S04 in FIG. 13). Then, the suction of the reactionsolution starts at the instant that the tip of the rinse chip 1701contacts the surface 1151 of the reaction solution 1141 (S05 in FIG.13). Since the cleaning fluid suction unit is already in operation asabove, the reaction solution is discharged from the reaction containerfirst, by which the cleaning efficiency is improved compared to caseswhere the cleaning fluid mixed with the reaction solution is circulatedin the reaction container. Further, if the rinse chip is soaked in thereaction solution when the reaction container is full of the reactionsolution, the reaction solution may overflow from the reactioncontainer, contaminate the analyzer, and deteriorate the reliability ofthe analyzer. This embodiment eliminates such a problem since thereaction solution has sufficiently been discharged from the reactioncontainer at the point when the lowering of the washing head iscompleted.

In order to prevent the base of the rinse chip 1701 from contacting thereaction region 1150 when the lowering of the washing head 1103 iscompleted (S06 in FIG. 13), a latch 1702 for positioning the rinse chip1701 by contacting the top of the reaction container 1140 is desired tobe formed in the upper part of the rinse chip 1701. The latch 1702,which covers and stops up the opening of the reaction container 1140,also prevents the reaction solution and the cleaning fluid fromoverflowing from the reaction container 1140 during the washingoperation. The side face 1703 of the rinse chip is desired to be cut ina shape like that of the side wall of the reaction container 1140 sothat the base of the rinse chip 1701 can get close to the bottom of thereaction container 1140.

When the discharge of the cleaning fluid is started (S06 and S07 in FIG.13), a flow of the cleaning fluid 1400 occurs at the bottom of thereaction container as indicated with the arrows 1710 a, 1710 b, 1710 c,1710 d and 1710 e in FIG. 18. When only the discharge pipe and thesuction pipe are used as in the fourth through sixth embodiments, it isdifficult to define the flow path of the cleaning fluid since thesurface of the cleaning fluid can move freely. Consequently, the controlof the flow velocity of the cleaning fluid is difficult. In contrast, byusing the rinse chip as in this embodiment, the flow path of thecleaning fluid flow can structurally be defined between the rinse chipand the bottom of the reaction container. This makes it possible toreduce the amount of the cleaning fluid used for the washing, whichcontributes to the reduction of the running cost. Incidentally, if abroadening flow path 1720 is formed on the discharge pipe's side asshown in FIG. 18(A), the flow velocity of the cleaning fluid becomeshigh in the discharge flow 1721 and low in the downstream flows 1710 a,1710 b and 1710 c. On the suction pipe's side, the flow velocity is highin the flows 1710 d and 1710 e since a flow channel 1730 with a smallcross-sectional area is formed between the rinse chip 1701 and thebottom of the reaction container 1140. The flow velocity distribution inthis case is indicated with a thick solid line 1806 in FIG. 19.

In comparison with the solid line 1801, even though the maximum flowvelocity decreased due to the reduction of the amount of flow, the flowvelocity increased at the points B and C. Therefore, the reactioncontainer can be washed and cleaned sufficiently without harming thereaction region.

In the case where the rinse chip is attached to the tips of the washingpipes, the rinse chip, which is larger than the tips of the washingpipes, is immersed in the reaction solution, and thus the cleaning ofthe washing head has to be conducted sufficiently in order to preventthe contamination. In this case, the rinse chip is desired to be formedof water-repellent material such as polyethylene terephthalate.

A rinse chip of a lateral channel type may also be employed as shown inFIG. 20.

In the example of FIG. 20, lateral channels 1810 and 1811, extendinglaterally from the discharge pipe 1101 and the suction pipe 1102, areformed in the rinse chip 1701. Thanks to the lateral channel 1810, thefluid discharged from the discharge pipe forms a flow 1801 that does notdirectly collide with the bottom of the reaction container, by whichdamage to the coating reagent 1150 is reduced and the detection accuracyis improved. Further, since the lateral channel 1810 is formed in ashape broadening toward the microchip base, the cleaning fluid flowsfrom the side to the microchip base uniformly like the cleaning fluidflows 1802 and 1803, which improves the washing efficiency. Also in thesuction, the cleaning fluid is sucked by the lateral channel 1811 in acontracting flow (e.g., cleaning fluid flow 1802). Consequently, auniform flow field is formed and the washing efficiency is improved.

DESCRIPTION OF REFERENCE CHARACTERS

-   100 reaction container-   161 reaction disk-   nozzle-   nozzle disk

The invention claimed is:
 1. A chemical analyzer comprising: a reactioncontainer setting table on which a plurality of reaction containers,each having an opening thereon are set; a pipetting mechanism forpouring a sample and a reagent separately from their respectivecontainers to ones of the reaction containers; an air ejection hole forejecting air to one of the reaction containers from above the reactioncontainer setting table so as to stir and mix the sample and the reagentin the one of the reaction containers; a detection mechanism fordetecting a result of a reaction of the sample and the reagent in theone of the reaction containers; a driving motor for moving the airejection hole or the reaction container setting table to change apositional relationship between the air ejection hole and the reactioncontainer setting table; at least one pressure sensor which is disposedwithin the reaction container setting table so as to sense pressure viaa pore formed through the reaction container setting table, wherein theat least one pressure sensor continuously detects pressure changes ofthe air ejected from the air ejection hole while a positionalrelationship between the air ejection hole and the at least one pressuresensor is changed by the driving mechanism; and a controller thatcompares a pressure measurement value detected by the at least onepressure sensor with a preset pressure threshold value and reports anoccurrence of a preset difference between the measurement value and thepreset threshold value when the occurrence of the preset differencebetween the measurement value and the preset threshold value isdetected.
 2. The chemical analyzer according to claim 1, furthercomprising: an incubator in which the reaction container setting tableand the air election hole are installed, wherein the air ejection holefaces downward and is disposed at an upper part of the incubator.
 3. Thechemical analyzer according to claim 1, further comprising: a flushingdisk which eliminates clogging of the air ejection hole.